Nucleoside analogues are an important class of therapeutic agents. More particularly, dioxolane nucleoside analogues in which a substituted 1,3-dioxolane is replacing the carbohydrate found in natural nucleoside have shown to have biological activity.
Dioxolane analogues were first reported by Belleau et al. in EP 0337713 published Oct. 19, 1989, in U.S. Pat. No. 5,041,449 issued Aug. 20, 1991 and U.S. Pat. No. 5,270,315 issued Dec. 14, 1993.
9-(β-D-2-hydroxymethyl-1,3-dioxolane-4-yl)-2,6-diaminopurine (β-D-DAPD) and 9-(β-D-hydroxymethyl 1,3-dioxolane-4-yl)-9-guanine (β-D-DXG) have been reported by Gu et al. (Antimicrob. Agents Chemother. (1999), 43(10), pp 2376-2382 and Nucleosides Nucleotides (1999), 18(4&5), pp 891-892) to have useful efficacy against HIV-1 in various cell system.
Additionally, it was also reported (Weitman et al Clinical Cancer Research (2000), 6(4), pp 1574-1578 and Giles et al Journal of Clinical Oncology (2001), 19(3), pp 762-771 and also Gourdeau et al Cancer Chemother. Pharmacol. (2001), 47(3), pp 236-240) that 1-(β-L-2-hydroxymethyl-1,3-dioxolane-4-yl)-cytosine (β-L-OddC, troxacitabine) have shown efficacy for the treatment of various forms of cancers (e.g. solid tumours, adult leukemia and lymphomas).
Dioxolane intermediates such as 2-Benzoyloxymethyl-[1,3]dioxolane-4-carboxylate esters are important intermediates used in the synthesis of dioxolane nucleoside analogues as described in PCT publication number WO 97/21706 by MANSOUR, Tarek et al. 19 Jun. 1997, PCT publications number WO 00/47759 by CIMPOIA, Alex et al. 17 Aug. 2000, and
PCT publication number WO 00/39143 by NGUYEN-BA, Nghe et al. 6 Jul. 2000. For the past years, literature has reported efforts directed toward development of bio-resolution methods. Enzymatic resolutions have the advantages of using catalytic amount of enzymes, being economical and reusable, and being environment friendly. Therefore, the identification of suitable enzymes for carrying diastereomeric resolution of 2-benzoyloxymethyl-[1,3]dioxolane-4-carboxylate esters is highly desirable.